crossing96/oncoscreening huggingface dataset:
Effects of Avelumab Maintenance on Advanced Urothelial Carcinoma: A Real-World Multicenter Study.	OBJECTIVES: Oncological outcomes in patients with urothelial carcinoma treated with avelumab maintenance therapy or conventional platinum-based first-line chemotherapy were compared in real-world practice. METHODS: Outcomes in patients with advanced urothelial carcinoma treated with platinum-based first-line chemotherapy without avelumab (chemo group, n = 300) or avelumab maintenance therapy (avelumab group, n = 85) between March 2004 and September 2024 were retrospectively evaluated. Overall survival (OS) in the chemo and avelumab groups was stratified by the number of cycles of first-line chemotherapy. The primary outcome was OS among patients without progressive disease (non-PD) at the cycle-4 assessment (the standard-switch cohort). The secondary outcome was OS among patients with non-PD at the cycles-2 to 3 assessment (the early-switch cohort). RESULTS: In the standard-switch cohort (non-PD at cycle 4), the chemo and avelumab groups comprised 122 and 47 patients, respectively; median OS was significantly longer with avelumab than with chemo (70 vs. 26 months; p = 0.015). In the early-switch cohort (non-PD at cycles 2-3), the chemo and avelumab groups comprised 104 and 35 patients, respectively; median OS was significantly longer with avelumab than with chemo (33 vs. 13 months; p = 0.002). A multivariable Cox regression analysis revealed that avelumab administration was significantly associated with a reduced risk of OS (hazard ratio, 0.37; p < 0.001). The retrospective design is a limitation of this study. CONCLUSION: Avelumab maintenance appeared to improve outcomes across cycles 2-3 and ≥ 4, though residual confounding cannot be excluded.	bladder
Comparison of adjuvant and neoadjuvant therapies for muscle invasive bladder cancer: A network meta-analysis.	Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease requiring multimodal treatment. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is standard, many patients experience recurrence, highlighting the need for improved perioperative strategies. The role of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings is promising, but the optimal approach remains unclear. This network meta-analysis (NMA) evaluates and ranks different perioperative treatments to identify the most effective strategy. We conducted a systematic review and NMA of 12 randomized controlled trials (RCTs) published between 1995 and 2024, including 5,026 patients with MIBC. Treatments analyzed included NAC ± immunotherapy, adjuvant immunotherapy, perioperative regimens, and dose-dense MVAC chemotherapy. Overall survival (OS) was the primary outcome. A Bayesian statistical model ranked treatments using SUCRA scores. The most effective strategy was NAC followed by surgery and adjuvant nivolumab (SUCRA: 99%, HR 0.43, 95% CrI 0.24-0.74). Perioperative durvalumab-based regimens (SUCRA: 82%) and dose-dense MVAC (SUCRA: 78%) also demonstrated significant benefit. Moderate heterogeneity (I² = 46%) was observed. These findings support integrating chemotherapy and immunotherapy into MIBC treatment. Adjuvant nivolumab after NAC and surgery appears most effective, while perioperative immunotherapy shows promise. Further trials are needed to refine treatment sequencing and optimize patient selection.	bladder
Optimizing Tissue Sampling Timing for Accurate Gene Expression Analysis.	The reliability of molecular diagnostic and prognostic tools is contingent on the quality of biospecimens, which are often collected during surgical procedures. This study investigated the impact of surgical manipulation on gene expression in the urinary bladder mucosa during radical cystectomy. Seventeen patients with urinary bladder cancer were enrolled, and paired pre- and post-surgery biopsies were analyzed. Pre-surgical biopsies were obtained in situ under anesthesia, while post-surgical biopsies were collected ex vivo following bladder removal. Total RNA was extracted, and gene expression was assessed using qPCR arrays, measuring the expression of 374 inflammation-related genes. The findings from the exploratory phase were further validated by analyzing key genes in an independent patient cohort using TaqMan(®) gene-specific assays. Exploratory analysis revealed significant differential expression in 27 genes, with key genes such as IL6, FOS, and PTGS2 being upregulated post-surgery. Validation of five selected genes in an independent cohort confirmed these findings. This study reinforces the necessity of accounting for surgery-induced alterations in gene expression when analyzing tissue samples collected intraoperatively. By elucidating the molecular impact of surgical interventions, this work provides critical insights for refining experimental methodologies and enhancing the interpretability of gene expression studies in clinical and research settings.	bladder
Dysregulated mitochondrial energy metabolism drives the progression of mucosal field effects to invasive bladder cancer.	Multiplatform mutational and gene expression profiling complemented with proteomic and metabolomic spatial mapping were used on the whole-organ scale to identify the molecular profile of bladder cancer evolution from field effects. Analysis of the mutational landscape identified three types of mutations, referred to as α, β, and γ. Time modeling of the mutations revealed that carcinogenesis may span 30 years and can be divided into dormant and progressive phases. The α mutations developed in the dormant phase. The progressive phase lasted 5 years and was signified by expanding β mutations, but it was driven to invasive cancer by γ mutations. The mutational landscape emerged on a background of disorganized urothelial differentiation, activated epithelial-mesenchymal transition, and enhanced immune infiltration with T-cell exhaustion. Complex dysregulation of mitochondrial energy metabolism with downregulation of oxidative phosphorylation emerged as the leading mechanism driving the progression of mucosal field effects to invasive cancer. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.	bladder
[Primary lymphomas in urinary bladder: a clinicopathological analysis of 23 cases].	"Objective: To investigate the clinicopathological features, diagnosis and differential diagnosis of primary bladder lymphoma. Methods: A retrospective study was conducted on 23 cases of primary bladder lymphoma diagnosed at Beijing Friendship Hospital of Capital Medical University between February 2010 and April 2024. The clinicopathological data were collected and analyzed, and literature was reviewed. Results: Among the 23 cases, 7 were male and 16 were female, with a male-to-female ratio of 1.0∶2.5. The median age was 65 (58, 71) years, ranged 38-84 years. The main clinical manifestation was painless visible hematuria, followed by frequent urination, urgency, and lower abdominal discomfort. Only one case presented with fever, and all cases primarily presented as bladder masses or lesions. The histological types included 17 cases of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (EMZL), 4 cases of diffuse large B-cell lymphoma (DLBCL), 1 case of ALK-negative anaplastic large cell lymphoma (ALCL), and 1 case of indolent NK-cell lymphoproliferative disease (INKLPD). EMZL exhibited relatively uniform morphology. Among them, 2 cases showed marked plasmacytic differentiation, 1 case had an increased number of large cells, 6 cases had residual germinal centers, and 2 cases presented with lymphoepithelial lesions. All cases demonstrated irregular FDC networks. DLBCL cells were larger in size; 3 cases showed diffuse infiltration, while 1 case had scattered, clustered distribution in a background of small lymphocytes,and with aberrant expression of GATA3. ALCL negative ALCL showed classic anaplastic morphology with ""kidney-shaped"" nuclei. INKLPD cells were of medium size and irregular in shape, with some cells containing eosinophilic granules in the cytoplasm. EBER in situ hybridization was negative. Conclusions: The primary histological types of bladder lymphoma are EMZL and DLBCL, with occasional cases of T-cell lymphoma and INKLPD. Clinical manifestations lack specificity and may overlap with inflammatory conditions or epithelial tumors. Both clinicians and pathologists should be aware of these rare diseases to facilitate accurate diagnosis and treatment."	bladder
Cisplatin-ineligible patients with muscle-invasive bladder cancer demonstrate poor long-term survival following immediate radical cystectomy.	OBJECTIVES: To compare survival and oncological outcomes of cisplatin-ineligible patients (Cis-I) and cisplatin-eligible (Cis-E) patients with muscle-invasive bladder cancer (MIBC) undergoing immediate radical cystectomy (IRC), as IRC is currently considered the standard-of-care for Cis-I patients with MIBC. PATIENTS AND METHODS: Data from patients with clinical (c)T2-4cN0-1M0 MIBC undergoing IRC, between 2006 and 2021, were retrospectively analysed from four tertiary care centres in the United States. Overall, recurrence-free and event-free survival were described using the Kaplan-Meier method and tested using the log-rank test. For context, we compared survival outcomes against those in Cis-E patients with MIBC undergoing IRC from the Southwest Oncology Group (SWOG)-8710 trial. RESULTS: Overall, 379 Cis-I and 125 Cis-E patients with cT2-4cN0-1M0 MIBC who underwent IRC were included. Cis-I patients included 44.8% cT3/4 vs 60% cT3/4 in the Cis-E group. Overall, 83.3% of Cis-I and 79.2% of Cis-E patients died during follow-up. The median event-free and overall survival were 12.1 and 14.5 months for the Cis-I group and 28.8 and 60.1 months for the Cis-E group (P < 0.001). [Correction added on 10 October 2025, after first online publication: The preceding sentence has been revised in this version.] Limitations include retrospective comparison of contemporary multi-institutional data with that of a randomised control trial. CONCLUSIONS: The Cis-I patients with MIBC undergoing IRC fared poorly, with a median overall survival of 14.5 (95% confidence interval 11.1-17.9) months, mostly due to non-cancer-related deaths. These results provide a benchmark for clinical trials exploring novel agents or alternative chemotherapy regimens in Cis-I patients with MIBC.	bladder
Multi-DECT Image-based Interpretable Model Incorporating Habitat Radiomics and Vision Transformer Deep Learning for Preoperative Prediction of Muscle Invasion in Bladder Cancer.	RATIONALE AND OBJECTIVES: The research aims to evaluate the effectiveness of a multi-dual-energy CT (DECT) image-based interpretable model that integrates habitat radiomics with a 3D Vision Transformer (ViT) deep learning (DL) for preoperatively predicting muscle invasion in bladder cancer (BCa). MATERIALS AND METHODS: This retrospective study analyzed 200 BCa patients, who were divided into a training cohort (n=140) and a test cohort (n=60) in a 7:3 ratio. Univariate and multivariate analyses were performed on the DECT quantitative parameters to identify independent predictors, which were subsequently used to develop a DECT model. The K-means algorithm was employed to generate habitat sub-regions of BCa. Traditional radiomics (Rad) model, habitat model, ResNet 18 model, ViT model, and fusion models were constructed from the 40, 70, and 100 keV virtual monochromatic images (VMIs) in DECT. The evaluation of all models used the area under the receiver operating characteristic curve (AUC), calibration curve, decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). The SHAP method was employed to interpret the optimal model and visualize its decision-making process. RESULTS: The Habitat-ViT model demonstrated superior performance compared to other single models, achieving an AUC of 0.997 (95% CI 0.992, 1.000) in the training cohort and 0.892 (95% CI 0.814, 0.971) in the test cohort. The incorporation of DECT quantitative parameters did not improve the performance. DCA and calibration curve assessments indicated that the Habitat-ViT model provided a favorable net benefit and demonstrated strong calibration. Furthermore, SHAP clarified the decision-making processes underlying the model's predicted outcomes. CONCLUSION: Multi-DECT image-based interpretable model that integrates habitat radiomics with a ViT DL holds promise for predicting muscle invasion status in BCa, providing valuable insights for personalized treatment planning and prognostic assessment.	bladder
Transient receptor potential vanilloid type 4 channels mediate bladder cancer cell proliferation, migration, and chemoresistance.	Bladder cancer (BLCA) is the second most common urologic cancer in the United States and worldwide and mostly affects the aging population. Despite several ongoing clinical trials, treatment paradigms for BLCA have not changed significantly. Here, we investigated the expression of transient receptor potential vanilloid type 4 (TRPV4) in patients with BLCA and its role in calcium influx, cell proliferation, and migration using normal human urothelial cells and BLCA cells. Bioinformatic analysis of the University of Alabama at Birmingham Cancer Data Analysis Portal and cBioPortal databases revealed that TRPV4 expression is significantly higher in human BLCA tissues than in normal adjacent tissues. Furthermore, TRPV4 expression was markedly elevated in early-stage BLCA and upregulated in muscle-invasive bladder cancer tissues. TRPV4 is expressed in both normal urothelial (SV-HUC-1) and BLCA (T-24) cells, and functional assays demonstrated enhanced TRPV4-mediated calcium influx in T-24 compared with SV-HUC-1 cells. T-24 cells exhibited higher spreading on extracellular matrix gels with increasing stiffness (0.2, 8, and 50 kPa) and exhibited a migratory phenotype compared to SV-HUC-1 cells. Pharmacological inhibition of TRPV4 significantly reduced proliferation and migration in T-24 cells but had minimal effects on normal cells. Finally, treatment with cisplatin significantly reduced TRPV4 protein levels and TRPV4-mediated calcium influx in chemosensitive UM-UC-3 cells but remained unchanged in chemoresistant T-24 cells, suggesting a potential role of TRPV4 in chemoresistance. In conclusion, TRPV4 may contribute to BLCA progression by regulating cell proliferation and migration and may impart resistance to chemotherapy. Targeting TRPV4 could present a novel therapeutic approach for managing BLCA progression and overcoming chemoresistance. SIGNIFICANCE STATEMENT: This study identified transient receptor potential vanilloid type 4 (TRPV4) as a critical driver of bladder cancer (BLCA) progression. TRPV4 gene expression is elevated in both early-stage and muscle-invasive BLCA tissues. Importantly, TRPV4 inhibition selectively reduces BLCA growth and motility. Furthermore, TRPV4 is downregulated by cisplatin in chemosensitive but not chemoresistant BLCA cells, underscoring its key role in bladder cancer chemoresistance. These findings position TRPV4 as a therapeutic target for enhancing BLCA treatment and overcoming drug resistance.	bladder
KDM6A deficiency promotes 5-aminolevulinic acid-mediated photodynamic therapy resistance in bladder cancer by suppressing ROS accumulation.	BACKGROUND: Non-muscle invasive bladder cancer (NMIBC) frequently recurs after transurethral resection of bladder tumors, necessitating a novel therapeutic approach. 5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) has emerged as a minimally invasive therapeutic approach; however, its long-term efficacy remains limited, and the mechanisms underlying ALA-PDT resistance are unclear. Lysine-specific demethylase (KDM) 6A, a tumor suppressor frequently mutated in NMIBC, has been implicated in cancer stemness and therapy resistance. OBJECTIVE: This study aimed to investigate the role of KDM6A deficiency in modulating ALA-PDT efficacy in bladder cancer. METHODS: KDM6A-knockout (KO) bladder cancer cell lines were established using CRISPR/Cas9-based gene editing. Cancer stemness was evaluated via sphere formation assays and expression of stem cell markers, while the cytotoxic effects of ALA-PDT were assessed through cell viability analysis. Protoporphyrin IX (PpIX) accumulation and reactive oxygen species (ROS) generation were examined using fluorescence microscopy and flow cytometry. RESULTS: KDM6A-KO cells exhibited significantly increased sphere-forming ability, enhanced stem cell marker expression, and greater resistance to ALA-PDT-induced cytotoxicity. Despite elevated PpIX accumulation in KDM6A-KO cells, ROS levels following ALA-PDT were significantly reduced. A negative correlation between KDM6A expression and ROS-scavenging enzymes expression, particularly SOD2 and GPX1, was confirmed both in public database analyses and in KDM6A-deficient cells. CONCLUSIONS: These findings indicate that KDM6A deficiency promotes cancer stemness and confers resistance to ALA-PDT in bladder cancer cells by suppressing ROS generation despite increased PpIX levels. This study provides new insights into the role of KDM6A in ALA-PDT resistance and may contribute to developing novel therapeutic and diagnostic strategies for NMIBC.	bladder
State-of-the-Art Imaging in Antibody-Drug Conjugate Treatment for Advanced Bladder Cancer.	Antibody-drug conjugates (ADCs) have revolutionized the treatment landscape for advanced bladder cancer, particularly enfortumab vedotin and trastuzumab deruxtecan, which target Nectin-4 and human epidermal growth factor receptor 2 (HER 2), respectively. These ADCs have shown substantial efficacy, improving survival in patients who have progressed after chemotherapy and immunotherapy. Imaging plays a pivotal role in ADC-based therapy, extending beyond diagnosis and staging to assessing treatment response, detecting recurrence, and evaluating toxicity. Computed tomography (CT), multiparametric magnetic resonance imaging (MRI), and fluorodeoxyglucose positron emission tomography (FDG-PET) are widely used for these purposes. Despite the efficacy of ADCs, resistance mechanisms such as antigen loss and payload resistance continue to pose challenges, necessitating the development of next-generation ADCs. Response assessment largely relies on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, with growing interest in multiparametric MRI for evaluating complete response in bladder lesions. Additionally, imaging helps identify ADC-related toxicities, including pneumonitis and gastrointestinal complications. Radiologists must be aware of these evolving therapeutic and imaging paradigms to optimize patient management. The integration of imaging with ADC-based treatment requires a multidisciplinary approach to improve outcomes. This review highlights the critical role of imaging in ADC therapy and underscores the need for radiologists to adapt to these advancements in bladder cancer treatment.	bladder
DNA Methylation in Bladder Cancer: Diagnostic and Therapeutic Perspectives-A Narrative Review.	Bladder cancer pathogenesis is closely linked to epigenetic alterations, particularly DNA methylation and demethylation processes. Environmental carcinogens and persistent inflammatory stimuli-such as recurrent urinary tract infections-can induce aberrant DNA methylation, altering gene expression profiles and contributing to malignant transformation. This review synthesizes current evidence on the role of DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) and the hypermethylation of key tumour suppressor genes, including A2BP1, NPTX2, SOX11, PENK, NKX6-2, DBC1, MYO3A, and CA10, in bladder cancer. It also evaluates the therapeutic application of DNA-demethylating agents such as 5-azacytidine and highlights the impact of chronic inflammation on epigenetic regulation. Promoter hypermethylation of tumour suppressor genes leads to transcriptional silencing and unchecked cell proliferation. Urine-based DNA methylation assays provide a sensitive and specific method for non-invasive early detection, with single-target approaches offering high diagnostic precision. Animal models are increasingly employed to validate these findings, allowing the study of methylation dynamics and gene-environment interactions in vivo. DNA methylation represents a key epigenetic mechanism in bladder cancer, with significant diagnostic, prognostic, and therapeutic implications. Integration of human and experimental data supports the use of methylation-based biomarkers for early detection and targeted treatment, paving the way for personalized approaches in bladder cancer management.	bladder
Effect of neoadjuvant chemotherapy on years of life lost in radical cystectomy-treated T2N0M0 bladder cancer patients.	INTRODUCTION: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is standard of care for T2N0M0 urothelial carcinoma of urinary bladder (UCUB) patients. However, the effect of NAC on years of life lost (YLL) in RC-treated T2N0M0 patients has never been quantified. METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2021), T2N0M0 UCUB patients aged 40-75 years treated with RC, with or without NAC, were included. Relying on Social Security Administration (SSA) life tables, an age/sex-matched control (Monte Carlo simulation) was simulated for each patient. Kaplan-Meier method was used to calculate average YLL until the age of 75 years between SEER cases and SSA simulated controls. RESULTS: Overall, 1511 (27.8%) T2N0M0 UCUB patients treated with RC + NAC and 3932 (72.2%) with RC alone were identified. Compared to simulated population controls, RC + NAC vs. RC alone patients exhibited 1.3 vs. 2.3 YLL. In sensitivity analyses according to age at diagnosis, the most pronounced YLL values were recorded in youngest patients (40-55 years): RC + NAC: 2.2 YLL vs. RC alone: 6.1 YLL. Intermediate YLL values were recorded in intermediate age patients (56-65 years): RC + NAC: 1.9 YLL vs. RC alone: 3.2 YLL. Finally, the least pronounced YLL values were recorded in oldest patients (66-75 years): RC + NAC: 0.4 YLL vs. RC alone: 0.7 YLL. Invariably, RC alone was associated with higher YLL values than RC + NAC. CONCLUSION: When YLL represented the endpoint, RC + NAC patients exhibited more favorable outcomes than RC alone patients. In both RC + NAC and RC alone groups maximal YLL applied to youngest individuals and decreased in proportion to increasing age.	bladder